Derivatives of 2,6-dodecadienoic acid

ABSTRACT

THIS INVENTION IS DIRECTED TO A PROCESS FOR PRODUCING 3ETHYL - 10,11 - EPOXY-2,6-DODECADIENOIC ACID DERIVATIVES WHICH ARE USEFUL IN KILLING AND PREVENTNG PROLIFERATION OF INSECTS BY UPSETTING THEIR HORMONE BALANCE FROM 3,7-DILOWER ALKYL-1,6-OCTAFIEN-3-OLS AND INTERMEDIATES THEREIN.

United States Patent O Int. Cl. C07d 1/12 US. Cl. 260-2473 2 ClaimsABSTRACT OF THE DISCLOSURE This invention is directed to a process forproducing 3- ethyl 10,11 epoxy-2,6-dodecadienoic acid derivatives whichare useful in killing and preventing proliferation of insects byupsetting their hormone balance from 3,7-dilower alky1-1,6octadien-3-olsand intermediates therein.

CROSS REFERENCE TO RELATED APPLICATIONS This application is a divisionalapplication of Ser. No. 691,246, filed Dec. 18, 1967 and now U.S. Pat.No. 3,513,176, issued May 19, 1970.

BACKGROUND OF THE INVENTION The activity of the methyl esters of,11-epoxy-3,11- dimethyl-7-ethyl-2,6-tridecadienoic and 10,1l-epoxy-3,7,1l-trimethyl-2,6-dodecadienoic acid for upsetting the hormone balance ofinsects to prevent them from growing and reproducing is well known.Furthermore, the use of these compounds as insecticides has stirredgreat interest since while these compounds are effective in killinginsects by upsetting their hormone balance, these compounds areconsidered harmless to animals that are of a higher order than insects.

These two compounds can be synthetically prepared either by a longcomplicated synthesis or from farnesol which is a C alcohol containingthree olefinic double bonds. In the process of preparing the methylester of 10,11 epoxy 3,7,11-trimethyl-2,fi-dodecadienoic acid, farnesolis first oxidized to farnesal which is then further oxidized tofarnesenic acid. The farnesenic acid is then esterified to give themethyl ester which is epoxidized at the terminal double bond to give thefinal product. It has been found that by epoxidizing the methyl ester offamesenic acid a mixture of products is formed. This occurs since epoxygroups form at all of the olefinic positions in the molecule and notonly at the desired terminal olefinic position. Therefore, the yield ofthe desired 10,11- epoxy compound which has the insecticide activity isvery low when produced by this process. Furthermore, workers in thefield have found that the separation of the desired 10,11-epoxy compoundfrom the various epoxy isomers produced by this process is verydifficult, requiring expensive equipment and handling techniques.

SUMMARY OF THE INVENTION In accordance with this invention, we havediscovered that when a 3-substituted-1,6-octadiene compound of thewherein R and R are lower alkyl is treated with an epoxidizing agent,epoxidation takes place only at the double bond in the 6-positionwithout atfecting the double bond in the l-position so as to produce acompound of the formula:

wherein R and R are as above.

It has been found that the conversion of compounds of the Formula Iabove to compounds of the Formula II above is carried out without undueformation of other epoxy isomers. In accordance with this invention, ithas been found that compounds of the Formula II above can be convertedinto insecticides of the formula:

R I'M CH3 wherein R and R are as above; A is selected from the groupconsisting of O 0 R3 COR2, -C--N and --CHgOR2 R is selected from thegroup consisting of hydrogen, lower alkyl, phenyl and dilower alkylamino lower alkyl; and R and R are lower alkyl and taken together withthe nitrogen atom a mono heterocyclic ring selected from the groupconsisting of S-membered rings and 6-rnembered rings and containing atthe most, one further hetero atom selected from the group consisting ofnitrogen, oxygen and sulfur.

Therefore this invention provides a simple and economic means forproducing in high yields insecticides which upset the hormone balance ofinsects so as to control their growth and reproduction while beingharmless to animals of a higher form than insects. Furthermore, theprocess of this invention eliminates the necessity for separatingvarious epoxy isomers.

The process of this invention produces known compounds such as10,11-epoxy-3,11-dimethyl-7-ethyl-2,6-tridecadienoic acid methyl esterand 10,11-epoxy-3,7,1ltrimethyl-2,6-dodecadienoic acid methyl ester.These known compounds upset the hormone balance of insects such asyellow mealworm (Tenebrio molz'tor) and the American cockroach(Periplaneta americana) to prevent them from growing and reproducing.

DETAILED DESCRIPTION OF THE INVENTION The numbering of the octadienechain is shown in Formula I above for the purposes of convenience.

As used throughout the application, the term lower alkyl comprehendsboth straight and branched chain saturated hydrocarbon groups containingfrom 1 to 6 carbon atoms such as methyl, ethyl, propyl, isopropyl, etc.

In accordance with this invention when R in compounds of the FormulaeIII and III-A is di-lower alkylamino-lower alkyl, the preferred di-loweralkylaminolower alkyl radicals are dimethylaminomethyl,diethylaminoethyl, dimethylaminoethyl, and dimethylaminopropyl. When incompounds of the Formulae III and III-A R and R are taken together withthe nitrogen atom to form a 5- or 6-membered heterocyclic ring having,at the most, one further hetero atom selected from the group consistingof sulfur, oxygen, and nitrogen, the preferred heterocyclic rings arepiperazinyl, pyrrolidinyl, morpholinyl, piperidinyl and thioazolidine.

In accordance with this invention, the insecticides of the Formula IIIare prepared from the compounds of the Formula I by means of thefollowing reaction scheme:

wherein R, R and A are as above; R, R" and R" are each aryl containingfrom 6 to 20 carbon atoms such as phenyl, tolyl, xylyl, mesityl,naphthyl, anthryl, biphenyl, azulyl or aralkyl containing from 7 to 20carbon atoms such as benzyl or an alkyl group containing from 1 to 20carbon atoms, e.g., methyl, ethyl, hexyl, octyl, decyl, etc., and X isthe anion of a mineral acid, e.g., Cl Br I HSO The conversion ofcompounds of the Formula I above, to compounds of the Formula II above,is carried out by any conventional epoxidation technique such astreating the compound of Formula I above with an epoxidizing agent. Anyconventional epoxidizing agent can be utilized in carrying out step (a)in accordance with this invention. Among the preferred epoxidizingagents are the per acids such as peracetic acid, perphthalic acid, etc.,or hydrogen peroxide. Generally, it is preferred to carry out thisreaction at a temperature of from about C. to about 60 C. though lowertemperatures can also be utilized. The reaction of step (a) can beconveniently carried out in Water. However, generally it is preferredthat this reaction be carried out in an inert organic solvent. Anyconventional inert organic solvent can be utilized. Among the inertorganic solvents which can be utilized are included toluene, benzene,hexane, diethyl ether, chloroform, methylene chloride, etc.

The epoxidation of a compound of the Formula I above proceeds by theformation of an epoxy group at the olefinic double bond at the6-position without effecting the double bond at the 1-position.Therefore, it has been found that epoxidation of the compound of FormulaI produces a 6,7-epoxy compound without any formation of the 1,2-epoxycompound. Hence, the conversion of compounds of the Formula I intocompounds of the Formula II by epoxidation is carried out with highyields and without the necessity of separating out isomers of thecompound of Formula II above.

The conversion of compounds of the Formula II above to compounds of theFormula IV above, as in step (b) is carried out by heating compounds ofthe Formula II above to a temperature of 120 C. to about 220 C. Thereaction of step (b) is carried out by heating the reactants alone or inthe presence of an inert organic solvent such as the solventshereinbefore mentioned. If a solvent is utilized, it is preferred tocarry out this reaction in the presence of high boiling inert organicsolvents, since if the low boiling solvents are utilized, pressure mustbe applied in order to carry out this reaction. In carrying out thereaction of step (b) temperatures of greater than 220 C. can beutilized, if desired. However, it has been found that no additionaladvantage is incurred by utilizing temperatures of greater than 220 C.Therefore, temperatures above 220 C. are seldom utilized in carrying outthis reaction step. When compounds of Formula II are heated to atemperature of at least C., decarboxylation and rearrangement of thecompound of Formula II occurs so that compounds of Formula IV above areproduced in high yields.

The reaction of (b) can, if desired, be carried out in the presence ofan aluminum tri-(lower alkoxide) catalyst. Any of the conventionalaluminum tri-(lower alkoxide) catalysts such as aluminumtri-(isopropoxide), aluminum trimethoxide can be utilized in thisreaction.

The conversion of compounds of the Formula IV above into compounds ofthe Formula III above can be carried out as in step (c) by reactingcompounds of the Formula IV above with a compound of the Formula V via aWittig reaction. This reaction is preferably carried out in the presenceof a solvent, i.e., an organic solvent substantially inert to thereactants, such as a lower alkanol, i.e., methan01, ethanol, etc.,dimethylforrnamide, acetonitrile, or benzene. The preferred solvents aremethanol and benzene. The reaction is conducted in the presence of astrong base such as an alkali metal hydride, e.g., sodium hydride,potassium hydride, an alkali metal amide, e.g., sodium amide, alkalimetal lower alkoxide, preferably sodium methoxide, or a solution of analkali metal hydroxide in a lower alkanol, e.g., KOH in methanol orethanol an aryl or alkyl Group I-A metallo organic compound whereinlithium, sodium, potassium, rubidium, caesium and francium are theintended metallo moieties, and wherein the preferred alkyl moieties arethe lower alkyl groups and the preferred aryl moieties are phenyl andlower alkylsubstituted phenyl groups, with phenyl lithium and butyllithium being preferred metallo organics. In carrying out the Wittigreaction, temperature and pressure are not critical, and this reactioncan be carried out at room temperature or at elevated temperatures. Onthe other hand, temperatures as low as 0 C. can be utilized.

In forming the compound of Formula V above, a compound of the formula:

XCH -A (VI) wherein X is a halogen and A is as above is reacted with aphosphine of the formula:

RR"R"P (VIfiA) wherein R, R" and R' are as above.

Among the preferred phosphines of the Formula ,VI-A are includedtriphenyl phosphine, trimethyl phosphine. This reaction to form thecompound of Formula V is carried out in the presence of a solvent suchas any of the aforementioned inert solvents. In carrying out thisreaction to form the compound of Formula V above temperature andpressure are not critical, and temperatures of 0 C. to C. or higher canbe utilized.

Compounds of Formula IV above can be converted into compounds of FormulaIII above by reaction, as in step (c1) with compounds of the Formula V-Aabove, via a Horner reaction. In carrying out the reaction of step(c-l), temperatures of 0 C. to 70 C. can be utilized. Generally, it ispreferred to carry out this reaction at room temperature and atmosphericpressure. However, elevated temperatures and pressure can be utilized ifdesired. Furthermore, this reaction is carried out in an inert organicsolvent medium in the presence of a base. Any conventional inert organicsolvent can be utilized such as benzene, toluene, dimethyl formamide,diethyl ether,

etc. Any of the bases hereinbefore mentioned in connection with reaction(c) can be utilized.

The compound of Formula VA is prepared by reacting the compound ofFormula VI with a compound of the formula:

P(OR )3 (VI-B) wherein R is as above.

This reaction is carried out at temperatures of from 100 C. to 150 C.Furthermore, the formation of the compound VI-B can be carried oututilizing any solvent. On the other hand, if desired, this reaction canbe carried out in the presence of any conventional high boiling solventsuch as Decalin, tetralin, etc.

In accordance with this invention, it has been found that compounds ofthe Formula IV possess valuable perfumistic properties which make themuseful as odorants in the compounding of perfumes and other scentedcompositions.

The compound of Formula I is prepared from a tertiary alcohol of theformula:

wherein R and R are as above and M is an alkali metal such as sodium,potassium or lithium.

The reaction of compounds of Formula VII with compounds of Formula VIIIto form compounds of Formula IX is carried out, in accordance with step(d), by heating a mixture composed of the compounds of Formula VII andcompounds of Formula VIII in the presence of aluminum tri-(loweralkoxide). The reaction of step (d) is effected by adding catalyticamounts of an aluminum tri-(lower alkoxide) to the mixture and heatingthe mixture, preferably with suflicient stirring, to a temperaturesufficiently high to cause a steady evolution of carbon dioxide and thelower alkyl alcohol which is formed during the reaction. The completionof the reaction is indicated by the cessation of the evolution of carbondioxide and the alcohol. In carrying out this reaction, temperaturesfrom l220 C. are utilized With l70200 C. being the preferred range. Thisreaction can be carried out in the presence of an inert organic solvent,preferably a solvent which has a boiling point of over 100 C. Solventswhich may be used include high boiling hydrocarbons or hydrocarbonfractions, e.g., Decalin, tetralin, mineral oil, petroleum ether, highboiling inert ethers, e.g., di-phenyl ether, etc. On the other hand, thereaction can take place without utilizing any solvent. Aluminum tri-(lower alkoxides) which are used as catalysts in this reaction include,for example, aluminum tri-(methoxide),

aluminum tri-(ethoxide), aluminum tri-(isopropoxide), aluminumtri-(n-butoxide), aluminum tri-(n-pentoxide), aluminumtri-(n-heptoxide), etc. It is preferred, however, to use an aluminumtri-(lower alkoxide) wherein the alkoxide radical contains from 2 to 4carbon atoms, such as aluminum tri-(isopro'poxide).

In carrying out the reaction of step (d) usually one mole of thecompound of Formula VII above is reacted with one mole of the compoundof Formula VIII above. However, if desired, the reaction of step (d) canbe carried out with a molar excess of either the compound of Formula VIIabove or the compound of Formula VIII above.

The conversion of compounds of Formula IX above to compounds of theFormula X above, as in step (e), is carried out by treating compounds ofFormula IX above with an alkali metal acetylide. Generally, it ispreferred to carry out this reaction in an inert organic or inorganicsolvent, such as liquid ammonia, toluene, di-ethyl ether, etc. Anyliquid solvent which is inert to the reactants can be utilized incarrying out this reaction. Furthermore, in carrying out this reaction,temperatures of from -'50 C. to 50 C. can be utilized with temperaturesof from -30 C. to room temperature being preferred.

Compounds of Formula X are converted into compounds of Formula XI, as instep (I) by hydrogenating compounds of the Formula X in the presence ofa palladium catalyst poisoned with lead [see, e.g., H. Lindlar, Helv.Chirn. Acta, 35, (1952)].

In accordance with this invention octadienes of the formula:

wherein R is a lower alkyl radical containing from 1 to 6 carbon atomsand R is a lower alkyl radical with the proviso that when R; containsfrom 1 to 4 carbon atoms, R contains at least two carbon atoms can beprepared from the tertiary alcohols of Formula VII. The compounds ofFormula XIA, because of their fine fragrance, are extremely useful asodorants in the preparation of perfumes and in the preparation of otherscented compositions.

The compounds of Formula XI above are converted to the compounds ofFormula I above by treating the compound of Formula XI above withdiketene or an acetoacetic acid ester. In treating the compound ofFormula XI with diketene, an alkaline catalyst is utilized. Anyconventional alkaline catalyst can be utilized in carrying out thisreaction. Typical catalysts which can be utilized in carrying out thisreaction include sodium alkoxides, such as sodium methoxide, sodiumisopropoxide and sodium ethoxide; tertiary amines, such as pyridine,triethylamine, etc.; alkali metal hydroxides, such as sodium hydroxideand potassium hydroxide. In carrying out the reaction with diketene, nosolvent need be present. However, if desired, any conventionalinertorganic solvent can be utilized in carrying out this reaction.Typical inert organic solvents which can be utilized include benzene,toluene, petroleum ether, etc. In carrying out the reaction of thecompounds of Formula XI above with diketene to produce a compound of theFormula I above, temperatures and pressures are not critical. However,temperatures from 040 C., preferably room temperature, are generallyemployed in carrying out this reaction.

In treating the compounds of the Formula XI above with an aceto aceticacid ester to produce a compound of the Formula I above, anyconventional acid or alkaline catalyst can be utilized. This reactioncan be carried out with or without an inert organic solvent. If an inertorganic solvent is utilized any of the conventional inert organicsolvents hereinbefore mentioned can be utilized. In carrying out thereaction of an aceto-acetic acid ester with the compound of Formula XIabove, temperature and pressure are not critical and this reaction canbe carried at room temperature and atmospheric pressure. However, caremust be taken to prevent the temperature during this reaction from goingover 90 C. since cracking of the compound of Formula I above will occur.Generally, it is preferred to utilize a temperature of from C. to 90 C.during this reaction. This reaction is carried out by the distillationof the alcohol that is formed during this reaction. If a high boilingalcohol is formed, the reaction is carried out under vacuum so that thedistillation of the alcohol proceeds below a temperature of 90 C.

If the compound of Formula XI-A is treated as in step (g), new and novelaceto-acetate compounds are obtained having the formula wherein R is alower alkyl radical containing from 1 to 6 carbon atoms and R is a loweralkyl radical with the proviso that when R, contains from 1 to 4 carbonatoms, R contains at least two carbon atoms.

The end products of Formula III can exist in eight different geometricstereo-isomeric forms, each geometric isomeric form having two opticalantipodes. This invention includes compounds of Formula III above havingeach of the possible geometric and optical configurations as well asmixtures, including racemates, thereof.

The process of this invention, can, if desired, be utilized to preparethe compound of Formula III in any of its various geometric isomericforms. For instance, in the reaction of step (d) the compound of FormulaIX is produced in two different geometric isomeric forms, which ifdesired, can be separated by any conventional method such as fractionaldistillation or vapor phase chromatography.

Also, the reaction of step (b) produces from a pure geometric isomericform of compound II the compound of Formula IV in two differentgeometric isomeric forms. These geometric isomers can also be separatedby conventional means such as fractional distillation or vapor phasechromatography. Furthermore, with respect to the reaction of step (c) or(c1) the compound of the Formula III is produced from a pure geometricisomeric form of compound IV by these reactions in two geometricisomeric forms. These two geometric isomeric forms can be separated byany conventional means such as those hereinbefore mentioned.

The following examples are illustrative but not limitative of thisinvention.

Example l.Preparation of 6-methyl-5-octen-2-one A three liter flask wasfitted with a stirrer, thermometer, 18 inch column packed with saddles,receiver, and a tube from the receiver leading to a Dry Ice trap and gasmeter. The flask was charged with 200.2 gms. of 3-methyl- 1-penten-3-ol,520.6 gms. of ethyl acetoacetate and 2 gms. of aluminum isopropoxide.The reaction mixture was heated and when the temperature reached 130 C.,the gas meter was connected. The reaction was then maintained at a pottemperature of 175-190 C. whereupon ethanol distilled from the reactionand carbon dioxide was evolved. When evolution of carbon dioxide ceased,the reaction mixture was cooled and then distilled at 4/1 reflux ratioto give 6-methyl-5-octen-2-one (n =1.4410).

Example 2.-Preparation of 3,7-dimethyl-6-nonen- 1-yn-3-ol 27.6 gms. ofsodium metal were dissolved in 420 cc. of liquid ammonia. Acetylene gasWas then bubbled in after passing through a Dry Ice trap. When the bluecolor was discharged, the rate of addition of acetylene was slowed and asoltuion of 140.2 gms. of 6-methyl-5-octen- 2-one in 140 cc. of diethylether was added over a period of one hour. Acetylene was bubbled intothe reaction mixture for two hours more. After stirring overnight, theammonia was allowed to evaporate While being replaced with ether. Whenvirtually all the ammonia was gone, the reaction mixture was poured intodilute sulfuric acid and ice. The ether layer was separated, washed withwater and sodium bicarbonate solution and dried over sodium sulfate.After filtration and evaporation of the ether in vacuo, the residue wasdistilled through an 8 inch Vigreaux column to give3,7-dimethyl-6-nonen-1-yn-3-ol (n =1.4621).

Example 3.Preparation of 3,7-dimethyl-1,6-

nonadien-3-ol 135 gms. of 3,7-dimethyl-6-nonen-1-yn-3-ol, 270 cc. ofhexane and 6.7 gms. of Lindlar catalyst were stirred under an atmosphereof hydrogen in a one liter flask at atmospheric pressure. When 96% ofthe theoretical volume of hydrogen had been consumed, the uptake ceased.After filtration and evaporation of solvent, the product was distilledthrough an 8 inch Vigreaux column to give 3,7-dimethyl-1,6-nonadien-3-ol.

Example 4.-Preparation of 3,7-dimethyl-1,6-nonadien- 3-yl acetoacetate Atwo liter flask was charged with 336.5 gms. of 3,7-dimethyl-1,6-nonadien-3-ol, 380 cc. pentane, 4 cc. pyridine and 4 cc. ofacetic acid. 185 gms. of diketene were placed in a dropping funnel. Onethird of the diketene was added to the other reactants. The temperaturewas maintained at 20-30 C. After one hour the remainder of the diketenewas added over a period of 2 /2 hours at 2030 C. The reaction mixturewas stored in the refrigerator overnight. It was then washed with coldwater, dried over Na SO filtered and concentrated in vacuo. Thetemperature was not allowed to exceed 50 C. The residue consisted of 504gms. of 3,7-dimethyl-l,6-nonadien-3-yl acetoacetate (n =1.4627).

Example 5.-Preparation of 3,7-dimethyl-6,7-epoxyl-nonen-B-ylacetoacetate To 3,7-dimethyl-l,6-nonadien-3-yl acetoacetate (504.7 gms.)2.8 liters of toluene, and 86.4 gms. of anhydrous sodium acetate wasadded 570.3 gms. of acetic acid solution containing 40 percent by weightperacetic acid. This addition was made during two hours at 2025 C. Afterstirring 3.5 hours at 2025 C., the reaction mixture was poured into 3 l.of cold water. The toluene layer was separated and washed with water,saturated sodium bicarbonate solution, 2% sodium thiosulfate solutionand water. After drying over sodium sulfate and filtering, the toluenesolutiOn was concentrated in vacuo to give 501.7 gms. of3,7-dimethyl-6,7-epoxy-l-nonen-3-yl acetoacetate as a mixture ofgeometric stereo-isomers (n =1.4632).

Example 6.Preparation of 6,10-dimethyl-9,10-epoxydodeca-5-en-2-one A oneliter flask was fitted with a stirrer, thermometer, dropping funnel anda condenser with a tube at the top leading to a Dry Ice trap and gasmeter. The dropping funnel was filled with 400 gms. of3,7-dimethyl-6,7-epoxy- 1-nonen-3-yl acetoacetate. To the flask wasadded 6 gms. of aluminum isopropoxide and one quarter of the contents ofthe dropping funnel. The reaction mixture was heated, and when thetemperature reached C., the gas meter was connected. At 180 C. evolutionof carbon dioxide was vigorous. When gas evolution began to subside, theremaining contents of the dropping funnel were added at such a rate asto maintain vigorous gas evolution at l90 C. Heating was continued untilgas evolution ceased. 35.1 liters of carbon dioxide was evolved. Thereaction mixture was then distilled through an 18 inch column packedwith saddles at a 4 to 1 reflux ratio to obtain6,10-dimethyl-9,lO-epoxydodeca-S-en-Z-one as a mixture of geometricstereoisomers.

The 6,10-dimethyl-9,10-epoxydodeca-S-en-Z-one had a very soft, sweetfloral note with a brier rose character.

Example 7.-Preparation of ethyl-3,7,11-trimethyl-10,11-

epoxy-2,6-tridecadienoate To a suspension of sodium hydride 56.7%dispersion in mineral oil (3.39 gms.) in 120 cc. of diethyl ether wasadded diethyl carbethoxymethyl phosphonate (18.8 gms.) during 25 minutesat 20-25 C. When hydrogen evolution ceased,6,l-dimethyl-9,10-epoxydodeca-5-en-2-one (17.9 gms.) in 20 cc. ofdiethyl ether was added during 30 minutes at 203 0 C. After stirring 2hours at 2030" C., the reaction mixture was partitioned between waterand ether. The ether layer was washed with water, dried over sodiumsulfate, filtered and concentrated in vacuo. The residue was distilledthrough a Vigreaux column givingethyl-3,7,11-trimethyl-10,11-epoxy-2,6-tridecadienoate as a mixture ofgeometric stereo-isomers (n =1.4753).

Example 8 3,7-dimethyl-1,6-octadien-3-yl acetoacetate was prepared fromthe reaction product of 3-methyl-1-buten-3-ol and ethyl acetoacetate bythe procedure given in Examples 1-4.

Example 9.1Preparation of 3,7-dimethyl-6,7-epoxy1- octen-3-ylacetoacetate using perphthalic acid Commercial sodium perborate (527gms.) was suspended in 2.5 liters of cold water. Phthalic anhydride (535gms.) was added at 0 C. After stirring 3 hours at 0 C., 30% sulfuricacid was added at 0 C. until the reaction mixture was acid to congo.3,7-dimethyl-1,6-octadien-3-yl acetoacetate (468 gms.) in 1 liter oftoluene was added, and the reaction mixture was allowed to warm to roomtemperature. After one hour the reaction mixture was poured into 3.5liters of saturated sodium bicarbonate solution. The toluene layer wasseparated and washed with saturated sodium bicarbonate solution, 2%sodium thiosulfate solution and water. After drying over sodium sulfateand filtering, the toluene solution was concentrated in vacuo to give400.9 gms. of 3,7-dimethyl-6,7-epoxy-1- octen-3-yl acetoacetate as amixture of geometric stereoisomers (n =1.4609).

Example 10.Preparation of 3,7-dimethyl-6,7-epoxy-1- octen-3-ylacetoacetate using peracetic acid To 3,7-dimethyl-1,6-octadien-3-ylacetoacetate (596 gms.), anhydrous sodium acetate (108 gms.) and toluene(3.5 liters) was added 40% peracetic acid (712 gms.) during 3 hours at2025 C. After stirring 3.5 hours at 20 25 C., the reaction mixture waspoured into 3 liters of cold water. The toluene layer was separated andwashed with water, saturated sodium bicarbonate solution, 2% sodiumthiosulfate and water. After drying over sodium sulfate and filtering,the toluene solution was concentrated in vacuo to give 513 gms. of3,7-dimethyl-6,7-epoxy-1- octen-3-y1 acetoacetate as a mixture ofgeometric stereoisomers (n =1.4606).

Example 1l.-Preparation of 6,10-dimethy1-9,l0-epoxyundeca-5-en-2-one Aone liter flask was fitted with a stirrer, thermometer, dropping funneland a condenser with a tube at the top leading to a Dry Ice trap and gasmeter. The dropping funnel was filled with 400 gms. of3,7-dimethyl-6,7-epoxy-locten-3-yl acetoacetate. To the flask was added6 gms. of aluminum isopropoxide and one quarter of the contents of thedropping funnel. The reaction mixture was heated and when thetemperature reached 130 C., the gas meter was connected. At 180-l90 C.evolution of carbon dioxide was vigorous. When gas evolution began tosubside, the remaining contents of the dropping funnel were added atsuch a rate as to maintain vigorous gas evolution at l80-190 C. Heatingwas continued until gas evolution ceased. 35.1 liters of carbon dioxidewas evolved. The reaction mixture was then distilled through an 18 inchcolumn of saddles at a 4 to 1 reflux ratio. 199 gms. of6,l0-dimethyl-9,10-epoxyundeca-S-en-Z-one was collected. The product wasa mixture of geometric stereo-isomers (n =1.46).

The 6,10-dimethyl-9,10-epoxyundeca-S-en-Z-one had a soft, sweet floralnote with a rose nuance.

Example 12.-Preparation of methyl-3,7,11-trimethyl-10,11-epoxy-2,6-dodecadienoate To a suspension of sodium hydride 5 6.7%dispersion in mineral oil (8.5 gms.) in 750 cc. of dimethylformamide wasadded dimethyl carbomethoxymethyl phosphonate (38.2 gms.) during onehour at 203() C. When hydrogen evolution ceased,6,10-dimethyl-9,l0-epoxyuudeca-5-en-2- one (42.0 gms.) was added during45 minutes at 20 30 C. After stirring four hours at 20-30 C., thereaction mixture was poured into cold water and extracted two times withhexane. The hexane extracts were washed with water, dried over sodiumsulfate, filtered and concentrated in vacuo. The residue was distilledthrough a Vigreaux column to give 29.9 gms. ofmethyl-3,7,1l-trimethyl-IO, 11-epoxy-2,6-dodecadienoate as a mixture ofgeometric stereo-isomers (11 1.4774) Example 13.Preparation ofethyl-3,7,1l-trimethyl-IO, 1 1-epoxy-2,6-dodecadienoate Example 14 3ethyl-7-methyl-6,7-epoxy-1-nonen-3-yl acetoacetate was prepared from thereaction product of 3-methyl-lpenten-B-ol and the ethyl ester of3-oxo-pentanoic acid by the procedure of Examples 1 through 5.

Example 15 3 ethyl-7-methyl-6,7-epoxy-l-nonen-3-yl acetoacetate wasconverted to 6-ethyl-10-methy1-9,lO-epoxy dodeca-5- en-2-cne by theprooess of Example 11 which was then converted to10,11-epoxy-3,11-dimethyl-7-ethyl-2,6-tridecadienoic acid methyl esterby the procedure of Example 12.

We claim:.

1. A process for preparing an epoxy compound of the formula:

wherein R and R are lower alkyl; A is selected from the group consistingof and CH2OR2 R is selected from the group consisting of hydrogen, loweralkyl, phenyl and dilower alkyl amino lower alkyl; and R and R are loweralkyl and taken together with the nitrogen atom a mono heterocyclic ringselected from the group consisting of S-membered rings and 6-memberedrings and containing at the most, one

' 1 1 further hetero atom selected from the group consisting ofnitrogen, oxygen and sulfur;

from an acetoacetate of the formula:

wherein R and R are as above;

comprising the following steps:

(a) treating said acetoacetate compound with an epoxidizing agent toform an epoxy acetoacetate compound of the formula:

wherein R and R are as above;

(b) heating said epoxy acetoacetate compound to a temperature of 120 C.to about 220 C. to form a keto compound of the formula:

wherein R and R are as above; reacting said keto compound with acompound of the formula:

group consisting of O 0 B3 II II O-OR2, ON and OHZORZ R is selected fromthe group consisting of hydrogen, lower alkyl, phenyl and dilower alkylamino lower alkyl; and R and R are lower alkyl and taken together 12with the nitrogen atom a mono heterocyclic ring selected from the groupconsisting of S-membered rings and 6-membered rings and containing atthe most, one further hetero atom selected from the group consisting ofnitrogen, oxygen and sulfur;

from an acetoacetate of the formula:

wherein R and R are as above;

comprising the following steps:

(a) treating said acetoacetate compound with an epoxidizing agent toform an epoxy acetoacetate compound of the formula:

wherein R and R are as above;

(b) heating said epoxy *acetoacetate compound to a temperature of C. toabout 220 C. to form a keto compound of the formula:

wherein R and R are as above; and (c) treating said keto compound with aphosphonate of the formula:

wherein R and A are as above.

References Cited FOREIGN PATENTS 1,138,037 10/1962 Germany.

OTHER REFERENCES Dahm, K. H. et al.: Jour. Amer. Chem. Soc. 89 (20)Sept. 27, 1967, pp. 5292-4.

Kimel, W., et al.: Jour. Am. Chem. Soc., vol. 65, No. 10, October 1943,pp. 19928.

NORMA S. MILESTONE, Primary Examiner US. Cl. X.R.

UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION Patent No.3'573'299 Dated March 30; 97

Inventor) Andrews, Kimel and Propper It is certified that error appearsin the above-identified patent and that said Letters Patent are herebycorrected as shown below:

[- Column 11, line 5, Claim 1 Column 11, line )1, Claim 1 are as above;"

should be are as above; and.

UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION Patent No.3,575,292 Dated Inventor-(a) PAGE 2 It is certified that error appearsin the above-identified patent and that said Letters Patent are herebycorrected as shown below:

should be 1 CH3 i=CH-CH 4:112 J: -o-3-ca -fi-CH-g Signed and sealed this2nd day of November 1971.

(SEAL) Attest:

EDWARD M.FLETCHER,JH. attesting Officer ROBERT GOTTSCHALK ActingCommissioner of Pat

